Fox Chase Cancer Center Researchers Investigate Use of Nanoengineered Stem Cells as ‘Trojan Horse’ for Targeted Drug Delivery

Swayam Prabha, MBA, PhD
Swayam Prabha, MBA, PhD, lead author on the study and an associate professor in the Cancer Signaling and Microenvironment research program, has a study published in Materials Today Bio.

PHILADELPHIA (March 22, 2023)—An ongoing challenge of cancer treatment is finding a way to use powerful chemotherapies to attack tumor cells while minimizing toxic side effects. A recent study by researchers at Fox Chase Cancer Center and the Lewis Katz School of Medicine at Temple University has demonstrated a potential new way to avoid this problem by using nanoengineered stem cells as a drug delivery system.

Nanoengineering refers to the use of stem cells on the nanoscale, which is used to measure some of the smallest objects—one nanometer is one billionth of a meter.

Previous clinical trials of mesenchymal stem cells (MSCs) found they were safe, but that they were not effective as a tool for cancer drug delivery because they didn’t target tumors efficiently. But the new study identified a different way of nanoengineering and loading the cells that improves their ability to home in on the tumor site and successfully deliver their drug payload.

“Based on what has been found in prior clinical trials with naive MSCs, which are not engineered in the way ours are engineered, we believe our MSCs will work better,” said Swayam Prabha, MBA, PhD, lead author on the study and an associate professor in the Cancer Signaling and Microenvironment research program at Fox Chase.

For the study, Prabha and the research team loaded MSCs with paclitaxel, a powerful chemotherapy drug. In addition to being a common frontline treatment for lung and other cancers, the choice had a personal connection for Prabha—it’s the drug one of her relatives received during treatment for ovarian cancer.

“Despite being a 17-year survivor, she still has nerve numbness and reduced mobility in her limbs,” said Prabha, who is also an associate professor at the Fels Cancer Institute for Personalized Medicine at the Katz School of Medicine. “It’s a great standard-of-care treatment, but we have to give such high doses that it leads to toxic side effects that can have an impact on the patient’s quality of life.”

Stem cells offer a potential solution because they have the ability to target the cancer cells while shielding themselves from attack. By acting as a “Trojan horse” and delivering drugs directly into the tumor, they could open the door for lower doses of some toxic medications like paclitaxel.

Previous clinical studies of the technology found that naturally occurring MSCs weren’t good enough at homing in on tumor cells to be a viable treatment option. However, for the new study, scientists used nanoengineering to load the MSCs with the paclitaxel molecule. They found that these engineered MSCs were more effective at killing tumors in mice and investigated further to understand why.

When they took a closer look at what was happening at the molecular level, they found that when the engineered MSC was loaded with the toxic drug, it triggered a stress response in the cell. This in turn caused the cell to produce higher levels of two proteins, one which protects the cell from damage and another which improves its tumor-homing ability.

“Our MSC actually acts as a sponge, absorbing the shock and reprogramming to its advantage to allow it to home in on the tumor and not get killed in the process,” Prabha said.

The results came as a surprise, she added, since other research has focused on finding ways of genetically modifying MSCs to increase these proteins, with limited success. “We never thought that our vector would have just an inherent ability to protect itself without us doing anything to it.”

Next, Prabha and her team hope to further enhance this “sponge effect,” making it more effective. They also want to test the technology in clinical trials with the hope of demonstrating improved homing in human tumors.

“In the big picture we are working towards the day that cancer patients don’t have all these side effects, especially limb numbness, and we don’t have to give cancer patients so much pain medication,” she said. “Ultimately our goal is to make patients’ lives better and give them a better quality of life.”

The study, “Incorporation of Paclitaxel in Mesenchymal Stem Cells Using Nanoengineering Upregulates Antioxidant Response, CXCR4 Expression and Enhances Tumor Homing,” was published in Materials Today Bio.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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